Project Summary Hydrogen sulfide (H2S) is an important signaling molecule with potent cytoprotective actions in cardiovascular systems. Current results indicate that modulation of H2S levels could have potential therapeutic value for a number of disease states such as vasodilation, anti-inflammation, and anti-oxidation. However, the exact mechanisms of action are still unclear and the actual H2S concentration/flux needed to exhibit the optimal protection in those disease models are to be determined. This lack of knowledge presents a major burden in the development of H2S based therapy. To solve this problem, research tools that can effectively detect H2S and specifically supply/remove H2S in biological samples are needed. In this application we plan to develop highly sensitive fluorescent probes for H2S detection. We will also develop novel H2S releasing agents and scavenging agents. The new chemicals will be used to determine the optimal H2S profiles for cardioprotection in models of myocardial ischemia/reperfusion (MI/R) injury and heart failure. This study will establish useful protocols guiding the development of H2S therapy.